Niche regulation of corneal epithelial stem cells at the limbus
Cell ResearchPublished 1 January 2007Open access
Wei Li, Yasutaka Hayashida, Ying‐Ting Chen, Scheffer C.G. Tseng
Citations310
SJR quartileQ1
SJR score8.74
SNIP3.79
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
This review summarizes relevant literature and formulates several key questions to guide future research into better understanding of the pathogenesis of limbal stem cell deficiency and further improvement of the tissue engineering of the corneal epithelium by focusing on the limbal niche.
Abstract
Among all adult somatic stem cells, those of the corneal epithelium are unique in their exclusive location in a defined limbal structure termed Palisades of Vogt. As a result, surgical engraftment of limbal epithelial stem cells with or without ex vivo expansion has long been practiced to restore sights in patients inflicted with limbal stem cell deficiency. Nevertheless, compared to other stem cell examples, relatively little is known about the limbal niche, which is believed to play a pivotal role in regulating self-renewal and fate decision of limbal epithelial stem cells. This review summarizes relevant literature and formulates several key questions to guide future research into better understanding of the pathogenesis of limbal stem cell deficiency and further improvement of the tissue engineering of the corneal epithelium by focusing on the limbal niche.
Keywords
Medicine
CellSeria cultivation of strains of human epidemal keratinocytes: the formation keratinizin colonies from single cell is
4,520 Citations1975James G. Rheinwatd, Howard Green
Human diploid epidermis epidermal cells have been successfully grown in serial culture and it is possible to isolate keratinocyte clones free of viable fibroblasts, and human diploids keratinocytes appear to have a finite culture lifetime.
Cellular Physiology and BiochemistryThe Versatile Role of microRNA-30a in Human Cancer
3,409 Citations2017Changqian Wang, Xiang Yang +2 more
The Journal of Experimental MedicineIsolation and functional properties of murine hematopoietic stem cells that are replicating in vivo.
2,901 Citations1996Margaret A. Goodell, Katja Brose +3 more
It is discovered that display of Hoechst fluorescence simultaneously at two emission wavelengths revealed a small and distinct subset of whole bone marrow cells that had phenotypic markers of multipotential HSC, which were shown in competitive repopulation experiments to contain the vast majority of HSC activity from murine bone marrow and to be enriched at least 1,000-fold for in vivo reconstitution activity.
Journal of Clinical InvestigationEpithelial-mesenchymal transition and its implications for fibrosis
2,282 Citations2003Raghu Kalluri, Eric G. Neilson
This review highlights recent advances in the process of EMT signaling in health and disease and how it may be attenuated or reversed by selective cytokines and growth factors.
Nature MedicineThe ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype
2,276 Citations2001Sheng Zhou, John D. Schuetz +9 more
Results show that expression of the Bcrp1/ABCG2 gene is an important determinant of the SP phenotype, and that it might serve as a marker for stem cells from various sources.
Journal of Clinical InvestigationEpithelial-mesenchymal transition and its implications for fibrosis
2,177 Citations2003Raghu Kalluri, Eric G. Neilson
ScienceDefining the Epithelial Stem Cell Niche in Skin
2,036 Citations2003Tudorita Tumbar, Géraldine Guasch +5 more
It is found that these cells rarely divide within their niche but change properties abruptly when stimulated to exit, and their transcriptional profile is determined, which, when compared to progeny and other SCs, defines the niche.
CellSocializing with the Neighbors
1,710 Citations2004Elaine Fuchs, Tudorita Tumbar +1 more
This review, which examines adult stem cell niches and their impact on stem cell biology, highlights the importance of understanding how stem cells interact with their microenvironment to establish and maintain their properties.
ScienceStem Cells and Their Niches
1,545 Citations2006Kateri Moore, Ihor R. Lemischka
The stem cell niche concept is discussed, recent progress is highlighted, and important unanswered questions are identified.
CellExistence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: Implications on epithelial stem cells
1,428 Citations1989George Cotsarelis, Shih-Zen Cheng +3 more
Using 3H-thymidine labeling, a subpopulation of corneal epithelial basal cells are identified in the peripheral cornea in a region called limbus that are normally slow cycling, but can be stimulated to proliferate in response to wounding and to a tumor promotor, TPA.
The Journal of Cell BiologyDifferentiation-related expression of a major 64K corneal keratin in vivo and in culture suggests limbal location of corneal epithelial stem cells.
1,395 Citations1986Alexander Schermer, Sharon Galvin +1 more
Keratin expression data suggest that the acidic 55K and basic 64K keratins represent markers for an advanced stage of corneal epithelial differentiation.
Proceedings of the National Academy of Sciencesp63 identifies keratinocyte stem cells
1,369 Citations2001Graziella Pellegrini, Elena Dellambra +7 more
It is shown by clonal analysis that p63 is abundantly expressed by epidermal and limbal holoclones, but is undetectable in paraclones, and will be of practical importance for the clinical application of epithelial cultures in cell therapy as well as for studies on epithelial tumorigenesis.
The LancetLong-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium
1,365 Citations1997Graziella Pellegrini, Carlo Enrico Traverso +4 more
It is shown that corneal progenitor cells are localised in the limbus, that cultured limbal cells generate cohesive sheets of authentic cornean epithelium, and that autologous cultured corneals restored the corNEal surface of two patients with complete loss of the Corneal-limbus epithelio.
Nature BiotechnologyCapturing and profiling adult hair follicle stem cells
1,282 Citations2004Rebecca Morris, Yaping Liu +7 more
It is shown that bulge cells in adult mice generate all epithelial cell types within the intact follicle and hair during normal hair follicle cycling and provide potential targets for the treatment of hair loss and other disorders of skin and hair.
Annual Review of Cell and Developmental BiologySTEM CELL NICHE: Structure and Function
1,218 Citations2005Linheng Li, Ting Xie
A comparative summary of the differences and commonalities of different stem cell niches in Drosophila ovary/testis and Caenorhabditis elegans distal tip as well as in mammalian bone marrow, skin/hair follicle, intestine, brain, and testis is compared.
Nature MedicineDye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species
1,099 Citations1997Margaret A. Goodell, Michael Rosenzweig +8 more
Dual-wavelength analysis of Hoechst dye-stained human, rhesus and miniature swine bone marrow cells reveals a small, distinct population of cells that efflux the dye in a manner identical to murine SP cells, suggesting the existence of a hitherto unrecognized population of hematopoietic stem cells that lack the CD34 surface marker classically associated with primitive hematopolietic cells.
OphthalmologyLimbal Autograft Transplantation for Ocular Surface Disorders
1,083 Citations1989Kenneth R. Keivyon, Scheffer C.G. Tseng
Clinical results in 21 patients with follow-up of 6 months or more have consistently shown improved visual acuity, rapid surface healing, stable epithelial adhesion without recurrent erosion or persistent epithelial defect, arrest or regression of corneal neovascularization, and probable increased success for lamellar or penetrating keratoplasty.
Nature GeneticsNotch1 functions as a tumor suppressor in mouse skin
972 Citations2003Michaël Nicolas, Anita Wolfer +8 more
The results indicate that Notch1 functions as a tumor-suppressor gene in mammalian skin and can inhibit β-catenin-mediated signaling.
New England Journal of MedicineReconstruction of Damaged Corneas by Transplantation of Autologous Limbal Epithelial Cells
930 Citations2000Ray Jui-Fang Tsai, Lien-Min Li +1 more
Transplantation of autologous lim bal epithelial cells cultured on amniotic membrane is a simple and effective method of reconstructing the corneal surface and restoring useful vision in patients with unilateral deficiency of limbal epithelium.
The Journal of Cell BiologyLocation and Clonal Analysis of Stem Cells and Their Differentiated Progeny in the Human Ocular Surface
722 Citations1999Graziella Pellegrini, Osvaldo Golisano +5 more
It is found that conjunctival keratinocytes with high proliferative capacity give rise to goblet cells at least twice in their life and, more importantly, at rather precise times of their life history, namely at 45–50 cell doublings and at ∼15 cellDoublings before senescence.
Survey of OphthalmologyThe amniotic membrane in ophthalmology
691 Citations2004Harminder S. Dua, José Álvaro Pereira Gomes +2 more
The reintroduction of amniotic membrane in ophthalmic surgery holds great promise; however, although it has been shown to be a useful and viable alternative for some conditions, it is currently being used far in excess of its true useful potential.
EyeConcept and application of limbal stem cells
649 Citations1989Scheffer C.G. Tseng
The basic concept of stem cells, the reported findings of limbal stem cells for corneal epithelium, and their therapeutic applications are reviewed to gain a more complete understanding and increase proficiency in treating these diseases.
Survey of OphthalmologyLimbal Stem Cells of the Corneal Epithelium
641 Citations2000Harminder S. Dua, Augusto Azuara‐Blanco
Stem cells have certain unique characteristics, which include longevity, high capacity of self-renewal with a long cell cycle time and a short S-phase duration, increased potential for error-free proliferation, and poor differentiation.
NatureRole of the Pericorneal Papillary Structure in Renewal of Corneal Epithelium
640 Citations1971Martin Davanger, A. Evensen
Corneal epithelium, nonetheless, has considerable healing capacity, which is achieved primarily by migration of epithelial cells, and should correspond to higher demands on the generative capacity of the corneal basal cells compared with skin.
OphthalmologyCytologlogic Evidence of Corneal Diseases with Limbal Stem Cell Deficiency
488 Citations1995Vilavun Puangsricharern, Scheffer C.G. Tseng
Impression cytology can be used to diagnose and monitor corneal diseases with limbal deficiency, which manifest distinct clinical problems and are generally poor candidates for penetrating keratoplasty.
New England Journal of MedicineTreatment of Severe Ocular-Surface Disorders with Corneal Epithelial Stem-Cell Transplantation
480 Citations1999Kazuo Tsubota, Yoshiyuki Satake +5 more
Transplantation of corneal epithelial stem cells can restore useful vision in some patients with severe ocular-surface disorders and limbal dysfunction.
Experimental Eye ResearchIdentification and characterization of limbal stem cells
471 Citations2005Ursula Schlötzer‐Schrehardt, Friedrich E. Kruse
While most putative SC markers label the majority of limbal basal cells and, therefore, may not distinguish SC from progenitor cells, only ABCG2 appears to be the most useful cell surface marker for the identification and isolation of corneal epithelial SC.
Proceedings of the National Academy of SciencesStem cell niches in the adult mouse heart
432 Citations2006Konrad Urbanek, Daniela Cesselli +10 more
The recognition of long-term label-retaining cells provides functional evidence of resident CSCs in the myocardium, indicating that the heart is an organ regulated by a stem cell compartment.
Stem CellsCharacterization of Putative Stem Cell Phenotype in Human Limbal Epithelia
423 Citations2004Zhuo Chen, Cintia S. de Paiva +4 more
This work suggests that the basal epithelial cells of the limbus are p63, ABCG2 and integrin α9 positive, and nestin, E‐cadherin, connexin 43, involucrin, K3, and K12 negative, with relatively higher expression of integrin β1, EGFR, K19, and enolase‐α.
Proceedings of the National Academy of SciencesIsoforms of ΔNp63 and the migration of ocular limbal cells in human corneal regeneration
400 Citations2005Enzo Di Iorio, V. Barbaro +4 more
The concept that the alpha isoform of p63 is necessary for the maintenance of the proliferative potential of limbal stem cells and their ability to migrate over the cornea is supported.
Nature GeneticsA novel homeobox gene PITX3 is mutated in families with autosomal-dominant cataracts and ASMD
393 Citations1998Elena V. Semina, Robert E. Ferrell +7 more
expression analysis of Pitx3 in the mouse supports a unique role in early ocular development, with later expression extending to the midbrain, tongue, incisors, sternum, vertebrae and limbs, and new evidence of the contribution of the RIEG/PITX gene family to the developmental program underpinning normal eye formation.
British Journal of OphthalmologyLimbal epithelial crypts: a novel anatomical structure and a putative limbal stem cell niche
390 Citations2005Harminder S. Dua
A novel anatomical structure has been identified at the human limbus, which demonstrates characteristics of being a stem cell niche, and is termed the limbal epithelial crypt.
CorneaHuman Allograft Limbal Transplantation for Corneal Surface Reconstruction
381 Citations1994Ray Jui-Fang Tsai, Scheffer C.G. Tseng
Preliminary results indicate that limbal allograft transplantation may be able to reconstruct a corneal surface that has undergone bilateral diffuse destruction, including the loss of limbal epithelial stem cells.
Experimental Eye ResearchCorneal epithelial stem cells at the limbus: looking at some old problems from a new angle
333 Citations2003Robert M. Lavker, Scheffer C.G. Tseng +1 more
The realization that corneal epithelial stem cells reside in the limbal zone provides explanations for several paradoxical properties of cornesal epithelium including its 'mature-looking' basal cells, the preponderance of tumor formation in theLimbal zone, and the centripetal cellular migration.
Stem CellsABCG2 Transporter Identifies a Population of Clonogenic Human Limbal Epithelial Cells
315 Citations2005Cintia S. de Paiva, Zhuo Chen +3 more
It is demonstrated thatABCG2 transporter was exclusively expressed by limbal basal cells and that the ABCG2‐positive and SP cells possess enriched stem cell properties, suggesting for the first time that ABCG 2 could serve as a marker to identify the putative limbal epithelial stem cells.
BioEssaysAnterior eye development and ocular mesenchyme: new insights from mouse models and human diseases
311 Citations2004Aleš Cvekl, Ernst R. Tamm
It is proposed that PAX6 is a key element that synchronizes the complex interaction of cell types of different origin, which are all needed for proper morphogenesis of the anterior eye.
The Ocular SurfaceHow Does Amniotic Membrane Work?
306 Citations2004Scheffer C.G. Tseng, Edgar M. Espana +9 more
This review describes how the actions inherently operate in utero and how amniotic membrane transplantation aims to recreate such a fetal environment to exert these actions by insulating the surgical site from the host environment.
Developmental BiologyPax-6 Is First Expressed in a Region of Ectoderm Anterior to the Early Neural Plate: Implications for Stepwise Determination of the Lens
292 Citations1994Huashun Li, Jun-Ming Yang +3 more
The Pax-6 gene encodes a DNA-binding transcription factor essential to normal development of the mammalian eye that is first expressed in a crescent-shaped region of future head ectoderm that adjoins the anterior margin of the early neural plate and the results raise the possibility that Pax- 6 may be involved in the early establishment of lens-competent regions within the head ectODerm.
PubMedLimbal stem cell deficiency: concept, aetiology, clinical presentation, diagnosis and management.
290 Citations2000H. S. Dua, JS Saini +2 more
Ocular conditions with abnormalities of ocular surface repair include pterygium, limbal tumours, aniridia, severe scarring following burns, cicatricial pemphigoid and Stevens-Johnson Syndrome, sequelae of mustard gas exposure and Herpes simplex epithelial disease, radiation keratopathy, contact lens induced keratopathic, neuroparalytic keratitis and drug toxicity.
PubMedHuman corneal basement membrane heterogeneity: topographical differences in the expression of type IV collagen and laminin isoforms.
285 Citations1995Alexander V. Ljubimov, Robert E. Burgeson +4 more
Investigating in detail corneal basement membrane (BM) composition and correlate it with the differentiation state of contributing cells found a novel type of spatial heterogeneity ("horizontal") in the EBM composition was found between the central cornea, limbus, and conjunctiva.
PubMedComparison of central and peripheral human corneal epithelium in tissue culture.
285 Citations1987B Ebato, J Friend +1 more
Comparisons of growth kinetics of limbal and peripheral human corneal epithelial cells in tissue culture indicate that human ocular limbal epithelium grows better in culture than does peripheral human Corneal encapsulation.
Proceedings of the National Academy of SciencesAn empty <i>Drosophila</i> stem cell niche reactivates the proliferation of ectopic cells
281 Citations2003Toshie Kai, Allan C. Spradling
Empty niches can persist, signal incoming cells, and support ectopic proliferation in stem cell loss, and may underlie some disease states.
Survey of OphthalmologyEx vivo expansion of limbal epithelial stem cells: amniotic membrane serving as a stem cell niche
276 Citations2003Martin Grueterich, Edgar M. Espana +1 more
This review summarizes the published literature data collectively explaining how amniotic membrane is an ideal biological substrate that can help maintain and support the expansion of limbal epithelial stem cells.
British Journal of OphthalmologyEx vivo preservation and expansion of human limbal epithelial stem cells on amniotic membrane cultures
274 Citations2002Daniel Meller
These data support the notion that AM cultures preferentially preserve and expand limbal epithelial stem cells that retain their in vivo properties of slow cycling, label retaining, and undifferentiation and supports the feasibility of ex vivo expansion of Limbal epithelium expansion for treating patients with total limbal stem cell deficiency using a small amount of donor limbal tissue.
Human Molecular GeneticsDomain disruption and mutation of the bZIP transcription factor, MAF,associated with cataract, ocular anterior segment dysgenesis and coloboma
271 Citations2002Robyn V. Jamieson
These findings further implicate MAF/Maf in mammalian lens development and highlight the role of the lens in anterior segment development, as well as providing a molecular demonstration of a germline break in a common fragile site.
PubMedIn vitro propagation of human ocular surface epithelial cells for transplantation.
255 Citations1993Kristina Lindberg, Mary-Michael Brown +3 more
Results support the concept that corneal epithelial stem cells are located in the limbus and indicate that cultured autologous limbal cells may function as grafts to permanently restore the cornean epithelium after severe ocular surface injury.
CorneaAmniotic Membrane as a Substrate for Cultivating Limbal Corneal Epithelial Cells for Autologous Transplantation in Rabbits
238 Citations2000Noriko Koizumi, Tsutomu Inatomi +4 more
Eyes that were grafted with amniotic membrane that contained cultivated epithelial cells, however, were all successfully epithelialized up to 5 days after surgery, suggesting that autologous transplantation of cultivated corneal epithelium is feasible by using acellular amniotics membrane as a carrier.
Journal of Cell ScienceOcular surface epithelia contain ABCG2-dependent side population cells exhibiting features associated with stem cells
234 Citations2005Murat T. Budak, Önder Alpdoğan +4 more
SP cells were characterized by extremely low light side scattering and contained a high percentage of cells that showed slow cycling prior to tissue collection; exhibited an initial delay in proliferation after culturing; and displayed clonogenic capacity and resistance to phorbol-induced differentiation; all features consistent with a stem cell phenotype.
Trends in Cell BiologyHoming and mobilization in the stem cell niche
233 Citations1999Anthony D. Whetton, Gerard J. Graham
Current knowledge of the adhesive, homing and proliferative influences acting on HSCs and progenitor cells is reviewed, highlighting the importance of molecular mechanisms regulating this two-way flow of stem cells.
PubMedThe Pax-6 homeobox gene is expressed throughout the corneal and conjunctival epithelia.
225 Citations1997Barba M. Koroma, Jun-Ming Yang +1 more
Data indicate that in addition to its role in the embryo, Pax-6 is expressed strongly in surface epithelia of the adult cornea and conjunctiva, suggesting that the gene may function by regulating structural or secretory specializations in cells of these tissues.
Bioscience ReportsAmniotic Membrane Transplantation for Ocular Surface Reconstruction
215 Citations2001S. C. G. Tseng
Amniotic membrane transplantation is being increasingly used as graft for various conjunctival and corneal diseases and as a patch in cases of chemical and thermal burns, refractory and recalcitrant keratitis, and most recently as an excellent substrate for expanding epithelial stem cells ex vivo.
EyeStem cell differentiation and the effects of deficiency
212 Citations2003Harminder S. Dua, Annie Joseph +2 more
None of the known haematopoietic stem cell markers point to any unique cell(s) that could be regarded as stem cells, supporting the notion that the corneal epithelium is served by ‘committed progenitors’ rather than by stem cells.
British Journal of OphthalmologyAmniotic membrane transplantation for partial limbal stem cell deficiency
210 Citations2001David F. Anderson
Amniotic membrane transplantation appears to be a safe and effective method of restoring a stable corneal epithelium for cases of partial limbal stem cell deficiency and can be considered as an alternative to limbal autograft or allograft.
FEBS LettersHuman limbal epithelium contains side population cells expressing the ATP‐binding cassette transporter ABCG2
208 Citations2004Katsuhiko WATANABE, Kohji Nishida +8 more
Data from fluorescence‐activated cell sorting and real‐time quantitative RT‐PCR analysis shows that harvested limbal epithelial cells contain SP cells expressing ABCG2, and indicates that ABCG1 positiveLimbal epithelium cells are putative corneal epithelial stem cells.
American Journal of OphthalmologyEpithelial transplantation for the management of severe ocular surface disease
194 Citations1997EJ Holland
A new classification of epithelial transplantation procedures for ocular surface disease is presented, and the experience with a keratolimbal allograft procedure for limbal stem cell deficiency is presented and recommendations for the indications and postoperative management are made.
Investigative Ophthalmology & Visual ScienceDifferent Cell Sizes in Human Limbal and Central Corneal Basal Epithelia Measured by Confocal Microscopy and Flow Cytometry
192 Citations2003André Romano, Edgar M. Espana +4 more
The data collectively demonstrate that the smallest cells are located in the limbal basal epithelium, indicating that the limbus contained a substantial proportion of very low FSC and SSC cells for which there was no corneal counterpart.
DifferentiationStem cells of the corneal epithelium lack connexins and metabolite transfer capacity
189 Citations1997Maja Matić, Igor N. Petrov +4 more
The incompetence of stem cells for gap junction-mediated cell-to-cell communication is demonstrated and may reflect the need of these unique cells to maintain a distinct intracellular environment.
Graefe s Archive for Clinical and Experimental OphthalmologyCryopreserved human amniotic membrane for ocular surface reconstruction
184 Citations2000Friedrich E. Kruse, Antonia M. Joussen +5 more
The technique for preservation which is most widely used for ophthalmological amniotic membrane transplantation significantly impairs viability and proliferative capacity and seems to function primarily as matrix and not by virtue of transplanted functional cells.
PubMedLimbal palisades of Vogt.
184 Citations1982Morton F. Goldberg, Anthony J. Bron
The palisades of Vogt are distinctive normal features of the human corneoscleral limbus and their interpalisadal epithelial rete ridges may serve as a repository for corneal epithelial cells and be important in both aging and diseases of the cornea.
OphthalmologyComparison of Limbal and Conjunctival Autograft Transplantation in Corneal Surface Reconstruction in Rabbits
182 Citations1990Ray Jui-Fung Tsai, Tung‐Tien Sun +1 more
It is indicated that complete destruction of the limbal zone resulted in corneal vascularization and conjunctivalization, and that limbal transplantation has a better efficiency than conjunctical transplantation in restoring such destroyed corneale surface.
Proceedings of the National Academy of SciencesMarker succession during the development of keratinocytes from cultured human embryonic stem cells
180 Citations2003Howard Green, Karen Easley +1 more
OphthalmologyPhenotypic study of a case with successful transplantation of ex vivo expanded human limbal epithelium for unilateral total limbal stem cell deficiency
178 Citations2002Martin Grueterich, Edgar M. Espana +3 more
The preservation of a limbal epithelial phenotype on the reconstructed corneal surface indicates that amniotic basement membrane provides a unique stromal environment conducive to the preservation and expansion of lim bal epithelial progenitor cells.
PubMedConjunctival transdifferentiation is due to the incomplete removal of limbal basal epithelium.
177 Citations1990Friedrich E. Kruse, J J Chen +2 more
The hypothesis that corneal epithelial stem cells are located in the limbus is supported and indicates that an incomplete removal of the basal limbal epithelium by n-heptanol leads to unvascularized corneas with conjunctival transdifferentiation.
OphthalmologyAmniotic membrane transplantation for partial and total limbal stem cell deficiency secondary to chemical burn
165 Citations2003José Álvaro Pereira Gomes, Myrna Serapião dos Santos +4 more
AMT seems to be an efficient adjunct for ocular surface reconstruction in chemical burns with PLD when performed in conjunction with limbal stem cell transplantation, it is also effective in most cases of TLD.
Proceedings of the National Academy of SciencesStem cell homing: Rolling, crawling, and nesting
165 Citations1998Peter J. Quesenberry, Pamela S. Becker
Hematopoiesis is the best-studied stem cell system; the progenitor hierarchy has been defined along with the cytokine requirements and transcriptional regulators.
Developmental DynamicsClonal analysis of patterns of growth, stem cell activity, and cell movement during the development and maintenance of the murine corneal epithelium
156 Citations2002J. Martin Collinson, Lucy X. Morris +9 more
It was found that maturation of the activity of limbal stem cells and the pattern of migration of their progeny are delayed for several weeks postnatally, and a new assay for limbal and corneal defects in mutant mice is provided.
Current Opinion in OphthalmologyAmniotic membrane surgery
152 Citations2001Kimberly C. Sippel, Joseph J.K. +1 more
Amniotic membrane transplantation (AMT) is currently being used for a continuously widening spectrum of ophthalmic indications and the superiority of AMT over other treatment modalities in many of these settings needs to be substantiated by controlled clinical trials.
PubMedConnexin 43 expression and proliferation of human limbal epithelium on intact and denuded amniotic membrane.
151 Citations2002Martin Grueterich, Edgar M. Espana +1 more
Data indicate that denudation of the devitalized amniotic epithelium to expose its basement membrane might be a microenvironmental cue to promote TAC differentiation.
BMC GeneticsHaploinsufficient Bmp4 ocular phenotypes include anterior segment dysgenesis with elevated intraocular pressure
148 Citations2001Bo Chang, Richard S. Smith +10 more
Bone morphogenetic proteins (BMPs) are a strong candidate to contribute to Axenfeld-Rieger anomaly, other developmental conditions associated with human glaucoma, and may allow identification of strain specific modifiers affecting a variety of ocular phenotypes.
DevelopmentDkk2 plays an essential role in the corneal fate of the ocular surface epithelium
143 Citations2006Mahua Mukhopadhyay, Marat Gorivodsky +5 more
It is shown that Dkk2-mediated repression of the Wnt/β-catenin pathway is essential to promote differentiation of the corneal epithelial progenitor cells into a non-keratinizing stratified epithelium.
The International Journal of Developmental BiologyOcular surface epithelial and stem cell development
134 Citations2004J. Mario Wolosin, Murat T. Budak +1 more
Track of expression changes in Cx43, the main gap junction protein expressed in both the pre-epithelial ectoderm and in the mature central corneal epithelium, indicates that a limbal stem cell phenotype starts developing very soon after lens vesicle invagination, in advance of the appearance of any recognizable anatomical sub-epIThelial limbal feature.
Current Eye ResearchExpression of keratins K12, K4 and K14 during development of ocular surface epithelium
133 Citations1994Michelle A. Kurpakus, M. Maniaci +1 more
The results suggest that the invagination of surface ectoderm to form the presumptive eyelid may be coupled to the initiation of differentiation of ocular surface epithelium.
Ophthalmic surgery, lasers & imaging retinaPeripheral Light Focusing by the Anterior Eye and the Ophthalmohelioses
132 Citations1991Minas T. Coroneo, N. Müller-Stolzenburg +1 more
A correlation between the locations of the foci of scattered incident light and the usual locations of pterygium and cortical cataract is demonstrated, suggesting the need for improved ocular protective devices, particularly ones that provide lateral protection of the eye against the increased ultraviolet insolation resulting from thinning of the ozone layer.
Proceedings of the National Academy of SciencesTransdifferentiation of corneal epithelium into epidermis occurs by means of a multistep process triggered by dermal developmental signals
131 Citations2005David J. Pearton, Ying Yang +1 more
Differentiated cells of the corneal epithelium are converted to hair, along with their associated stem cells, then interfollicular epidermis, by means of a multistep process triggered by dermal developmental signals.
DevelopmentAdult corneal epithelium basal cells possess the capacity to activate epidermal, pilosebaceous and sweat gland genetic programs in response to embryonic dermal stimuli
131 Citations2000Corinne Ferraris, Geneviève Chevalier +3 more
The results show that adult central corneal cells are able to respond to specific information originating from embryonic dermis, and provide the first evidence that a distinct TA cell population can be reprogrammed.
Stem CellsLimbal Epithelial Side-Population Cells Have Stem Cell–Like Properties, Including Quiescent State
123 Citations2005Terumasa Umemoto, Masayuki Yamato +4 more
The possibility that quiescent limbal epithelial SP cells may represent an extremely immature stem cell population compared with currently defined epithelial stem or progenitor cells is presented.
British Journal of OphthalmologyMorphological characteristics of the limbal epithelial crypt
122 Citations2006Vijay Shanmuganathan, Toshana L. Foster +6 more
The LEC contains a unique sub-population of cells expressing several characteristics that are consistent with it representing a putative stem cell niche, and is sparse but a consistent finding in the human corneo-scleral limbus.
Current Eye ResearchConjunctival epithelial cells do not transdifferentiate in organotypic cultures: expression of K12 keratin is restricted to corneal epithelium
121 Citations1994Willie Y. W. Chen, Mei Mei Mui +3 more
Bioscience ReportsSuccessful Reconstruction of Damaged Ocular Outer Surface in Humans Using Limbal and Conjuctival Stem Cell Culture Methods
120 Citations2003Veena Sangwan, Geeta K. Vemuganti +2 more
Ulastructural, histological, biochemical and immunological assays establish the identity of the cells and the tissue formed, and to graft the resulting viable and transparent epithelium to 125 needy human patients with success.
CorneaThe Immunohistochemical Composition of the Human Corneal Basement Membrane
118 Citations1996Antti Tuori, Hannu Uusitalo +3 more
The present results give new information on the Ln chain distribution and show that the BM of the corneal epithelium differs from that of surrounding epithelia by the lack of collagen type IV.
Investigative Ophthalmology & Visual ScienceCharacterization and Distribution of Bone Marrow–Derived Cells in Mouse Cornea
116 Citations2005Takahiro Nakamura, Fumihiko Ishikawa +8 more
Investigation of BM cells and BM-derived hematopoietic stem/progenitor cells from enhanced GFP (eGFP) transgenic mice found that some of these cells are BM- derived antigen-presenting cells such as dendritic cells and macrophages.
Investigative Ophthalmology & Visual ScienceStromal Niche Controls the Plasticity of Limbal and Corneal Epithelial Differentiation in a Rabbit Model of Recombined Tissue
116 Citations2003Edgar M. Espana, Tetsuya Kawakita +5 more
Results strongly indicate that the limbal stroma modulates epithelial differentiation, proliferation and apoptosis in the direction favoring stemness, whereas the corneal stroma promotes differentiation.
The International Journal of Biochemistry & Cell BiologyEvolving concepts on the pathogenic mechanisms of aniridia related keratopathy
114 Citations2004Kanna Ramaesh, Thaya Ramaesh +2 more
The potential mechanisms that may underlie the pathogenesis of aniridia related keratopathy are reviewed and it is suggested that the proliferative potential of the corneal limbal stem cells may not primarily be impaired.
EyeThe epithelial basement membrane zone of the limbus
114 Citations1989Ilene K. Gipson
Differences in adhesion structure pattern in limbus may indicate that this surface has less abrasion pressure from the lids or that the convoluted interdigitation of cytoplasmic processes with the stroma compensates for the smaller number of hemidesmosomes.
Archives of OphthalmologyHuman Limbal Progenitor Cells Expanded on Intact Amniotic Membrane Ex Vivo
114 Citations2002Martin Grueterich
The hypothesis that intact amniotic membrane preferentially preserves and expands Cx43- negative, keratin K3-negative, and GJIC-deficient limbal epithelium, a phenotype resembling that of stem cell-containing limbal basal epithelial cells in vivo, is supported.
Stem CellsHuman Side Population Keratinocytes Exhibit Long-Term Proliferative Potential and a Specific Gene Expression Profile and Can Form a Pluristratified Epidermis
114 Citations2005Gaëlle Larderet, Nicolas O. Fortunel +7 more
SP human keratinocytes isolated from primary cultures exhibited both short‐ and long‐term high proliferative potential, formed a pluristratified epidermis, and were characterized by a specific gene expression profile.
The Ocular SurfaceAmniotic Membrane Transplantation in the Management of Severe Ocular Surface Disease: Indications and Outcomes
111 Citations2004Charles S. Bouchard, Thomas John
This review has attempted to assess the indications and outcomes of AM transplantation based on 661 cases reported in the peer-reviewed literature and found successful outcome was defined as the healing of an epithelial defect over a specified time period and the lack of induced motility disturbance.
Progress in Retinal and Eye ResearchStem cells and differentiation stages in the limbo-corneal epithelium
111 Citations2000J. Mario Wolosin, Xiaoling Xiong +3 more
Journal of Biological ChemistryCharacterization and chromosomal localization of the cornea-specific murine keratin gene Krt1.12.
104 Citations1994Chia‐Yang Liu, Guang Zhu +8 more
Sequence analysis indicates that the transcripts derived from alternative splicing and/or the alternative promoter do not have a long open reading frame for keratin or keratin-like molecules.
Journal of Cell ScienceRegional variation in distribution of egf receptor in developing and adult corneal epithelium
103 Citations1993James D. Zieske, Michael Wasson
Cells with high potential for proliferation, i.e. limbal basal cells and all basal cells in developing rats, express high epidermal growth factor receptor levels, suggest that cells to be rapidly stimulated by growth factors to undergo cell division during development and following wounding in adult corneas.
CorneaEffect of Stromal Inflammation on the Outcome of Limbal Transplantation for Corneal Surface Reconstruction
100 Citations1995Ray Jui-Fang Tsai, Scheffer C.G. Tseng
Results indicate that intenseStromal inflammation associated with disease chronicity or additional stromal damage by lamellar keratectomy can interfere with the capability of limbal grafts to attain normal corneal epithelial proliferation and differentiation.
Journal of Investigative Dermatology Symposium ProceedingsCorneal Epithelial Stem Cells: Past, Present, and Future
96 Citations2004Tung‐Tien Sun, Robert M. Lavker
The limbal/stem cell concept provides explanations for several paradoxical properties of corneal epithelium including the predominance of tumor formation in the limbal zone, the centripetal migration of peripheralCorneal cells toward the central cornea, and the "mature-looking" phenotype of the cornean basal cells.
Experimental Eye ResearchMelanocytes in the corneal limbus interact with K19-positive basal epithelial cells
94 Citations2005Kazunari Higa, Shigeto Shimmura +3 more
Melanocytes and K19 (+) epithelial cells may form a functional network similar to the melanin unit of the skin, and were identified by MART1, an antigen specific to melanocyte-lineage cells.
Developmental BiologyAdult Corneal Limbal Epithelium: A Model for Studying Neural Potential of Non-Neural Stem Cells/Progenitors
93 Citations2002Xing Zhao, Ani V. Das +5 more
The study draws attention toward the necessity for rigorous characterization of transdifferentiation and offers a model for characterizing neural potential of heterologous stem cells/progenitors.
PubMedFoxe3 haploinsufficiency in mice: a model for Peters' anomaly.
91 Citations2002Mattias Ormestad, Åsa Blixt +4 more
Although causality could not be shown in the human case, the presence of a rare, nonconservative substitution in FOXE3 of a patient with Peters' anomaly is interesting, in light of the phenotypic similarities with the mutant mice.
PubMedLymphocytes and Langerhans cells in the normal human cornea.
90 Citations1985L Vantrappen, Karel Geboes +3 more
The distribution of B- and T-lymphocytes, of OKIa positive cells, and of HLA-ABC antigens in the normal cornea was investigated using monoclonal antibodies.
Proceedings of the National Academy of SciencesSide population in adult murine epidermis exhibits phenotypic and functional characteristics of keratinocyte stem cells
89 Citations2006Richard P. Redvers, Amy Li +1 more
It is shown that the epidermal SP contains the most potent keratinocyte stem cell population in skin epithelium, consistent with a primitive cell type.
Stem CellsFormation of Neurons by Non‐Neural Adult Stem Cells: Potential Mechanism Implicates an Artifact of Growth in Culture
89 Citations2006Adam P. Croft, Stefan Przyborski
Evidence is presented that shows that cultured bone marrow‐derived stem cells express neural proteins and form structures resembling neurons under defined growth conditions, and it is demonstrated that these changes in cell structure and neural protein expression are not consistent with typical neural development.
Experimental Eye ResearchExpression and tissue distribution of p63 isoforms in human ocular surface epithelia
86 Citations2005Satoshi Kawasaki, Hidetoshi Tanioka +3 more
The results suggest that DeltaNp63alpha is the most dominant isoform within human ocular surface epithelia, and this isoform may contribute, at least in part, to the maintenance of cell proliferative capacity within the ocular surfaces of p63.
…